The onset of sleep disturbances and their associations with anxiety after acute high-altitude exposure at 3700 m.

Sleep disturbances and psychiatric repercussions pose great challenges at high altitude; however, few studies have investigated sleep disturbance and anxiety profiles and their associations after acute exposure in consecutive patients. Thus, we aimed to study the profiles of sleep disturbances in consecutive patients after high-altitude exposure and the association of such disturbances with anxiety. A total of 668 participants were recruited at sea level and 3700 m. The trials were performed at sea level (1 week prior to a 2-h flight to a high-altitude destination) and at 3700 m (24, 72, and 168 h). Sleep disturbances were assessed by self-reported sleep patterns and scores on the Athens Insomnia Scale (AIS). State anxiety was assessed using the Self-Rating Anxiety Scale (SAS). In our study, the incidence of sleep disturbances increased significantly after acute high-altitude exposure (65.3%, 434/668) and then gradually decreased after 72 h (50%, 141/282) and 168 h (44%, 124/282). The sleep assessments AIS [2.0 (4.0) vs. 4.0 (5.0)] and ESS [4.0 (4.0) vs. 5.0 (5.0)] increased significantly (p < 0.05). Also, the SAS increased significantly from 26.25 (3.75) to 28.75 (7.5). The SAS was significantly high in sleep disturbance group [31.25 (7.5) vs. 27.5 (5), p < 0.001] than in the non-sleep- disturbance group. The baseline SAS and AIS scores were significantly higher in participants with sleep disturbances than in those without (p < 0.01). Age, baseline insomnia, sleepiness, fatigue, and higher SAS were predictors of sleep disturbances in univariate regression (all p values < 0.05). However, only an older age (p = 0.045) and a higher baseline SAS (p = 0.018) remained independent predictors of sleep disturbances. Our findings indicated that acute high-altitude exposure triggers the onset of sleep disturbances, which are closely associated with anxiety. Furthermore, baseline state anxiety and age are independent predictors of sleep disturbances at high altitude.

MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway.

BACKGROUND: Neural precursor cell (NPC) migration toward lesions is key for neurological functional recovery. The neovasculature plays an important role in guiding NPC migration. MicroRNA-210 (miR-210) promotes angiogenesis and neurogenesis in the subventricular zone and hippocampus after cerebral ischemia; however, whether miR-210 regulates NPC migration and the underlying mechanism is still unclear. This study investigated the role of miR-210 in NPC migration. METHODS AND RESULTS: Neovascularization and NPC accumulation was detected around ischemic foci in a mouse model of middle cerebral artery occlusion (MCAO) and reperfusion. Bone marrow-derived endothelial progenitor cells (EPCs) were found to participate in neovascularization. miR-210 was markedly upregulated after focal cerebral ischemia/reperfusion. Overexpressed miR-210 enhanced neovascularization and NPC accumulation around the ischemic lesion and vice versa, strongly suggesting that miR-210 might be involved in neovascularization and NPC accumulation after focal cerebral ischemia/reperfusion. In vitro experiments were conducted to explore the underlying mechanism. The transwell assay showed that EPCs facilitated NPC migration, which was further promoted by miR-210 overexpression in EPCs. In addition, miR-210 facilitated VEGF-C (vascular endothelial growth factor C) expression both in vitro and in vivo. Moreover, the luciferase reporter assay demonstrated that miR-210 directly targeted the 3' untranslated region of SOCS1 (suppressor of cytokine signaling 1), and miR-210 overexpression in HEK293 cells or EPCs decreased SOCS1 and increased STAT3 (signal transducer and activator of transcription 3) and VEGF-C expression. When EPCs were simultaneously transfected with miR-210 mimics and SOCS1, the expression of STAT3 and VEGF-C was reversed. CONCLUSIONS: miR-210 promoted neovascularization and NPC migration via the SOCS1-STAT3-VEGF-C pathway.

Physiological and psychological factors associated with onset of high-altitude headache in Chinese men upon acute high-altitude exposure at 3700 m.

Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.

A higher baseline somatization score at sea level as an independent predictor of acute mountain sickness.

OBJECTIVE: The current study aimed to identify the predictive values of psychological factors that are evaluated by the Symptoms Checklist-90 (SCL-90) for acute mountain sickness (AMS). METHODS: The subjects (n=285, non-acclimatized young Chinese men), who were recruited in July 2013, completed a case report questionnaire. In addition, their vital signs (heart rate [HR], blood pressure and pulse oxygen saturation) were measured, and their psychological factors were examined using the SCL-90 at sea level. AMS was diagnosed using the Lake Louise self-assessment scoring system in the morning of the second day after their arrival at 3450m. RESULTS: Of the nine factors of the SCL-90, the AMS patients (AMS score≥3) were characterized by significantly higher scores for baseline somatization [14.0 (5.0) vs. 13.0 (3.0), p<0.001], obsession-compulsion, depression, anxiety and hostility compared with the non-AMS group (all p values<0.05). Spearman's correlation analyses revealed associations between AMS scores and somatization (r=0.316, p<0.001), depression, anxiety, obsession-compulsion, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation and psychoticism scores (all p values<0.001). Although all nine factors were associated with AMS in a univariate regression (all p<0.05), a further adjusted logistic regression analysis indicated that only baseline somatization score (odds ratio=1.129, p=0.001) was an independent predictor of AMS. Furthermore, some non-AMS often-occurred symptoms (paresthesia, shortness of breath, reduced activity and tinnitus) were also found to be associated with the baseline SCL-90 scores. CONCLUSION: AMS is correlated with the baseline somatization score at sea level, which was measured using the SCL-90. A higher baseline somatization score is also an independent predictor of AMS.

Principal Component Analysis and Risk Factors for Acute Mountain Sickness upon Acute Exposure at 3700 m.

OBJECTIVE: We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors. METHODS: The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses. RESULTS: The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS. CONCLUSIONS: Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS.

Hemodynamic characteristics of high-altitude headache following acute high altitude exposure at 3700 m in young Chinese men.

BACKGROUND: This study aimed to identify the systemic and cerebral hemodynamic characteristics and their roles in high-altitude headache (HAH) among young Chinese men following acute exposure. METHODS: The subjects (n = 385) were recruited in June and July of 2012. They completed case report form questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and transcranial Doppler examinations at 3700 m following a two-hour plane flight. A subgroup of 129 participants was examined at two altitudes (500 and 3700 m). RESULTS: HAH was characterized by increased HR and cardiac output (CO) and lower saturation pulse oxygen (SpO(2)) (all p < 0.05). The change in tricuspid regurgitation was also different between the HAH positive (HAH+) and HAH negative (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (V(m)), systolic (V(s)) and diastolic (V(d)) velocities in the basilar artery (BA; all p < 0.05) and a faster V(d) ( 25.96 ± 4.97 cm/s vs. 24.76 ± 4.76 cm/s, p = 0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also significantly different between the two groups. The pulsatility index (PI) and resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or right MCA in different regressions) were independent predictors for HAH, whereas CO/HR and ΔV(d) (V(d) difference between bilateral VAs) were independent risk factors for HAH at 3700 m. CONCLUSIONS: HAH was characterized, in part, by increased systemic hemodynamics and posterior cerebral circulation, which was reflected by the BA and left VA velocities, and lower arterial resistance and compliance. Furthermore, baseline CO and V(m) in left VA or right MCA at sea level were independent predictors for HAH, whilst bilateral VA asymmetry may contribute to the development of HAH at high altitude.

Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness.

OBJECTIVE: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS). METHODS: A total of 600 adult men were recruited. Subjects' subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured. RESULTS: Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314-1.464, P<0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS. CONCLUSION: Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS.

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men.

BACKGROUND: The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude. METHODS: A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured. RESULTS: Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28-1.51, P<0.001). CONCLUSION: The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects.

Cerebral hemodynamic characteristics of acute mountain sickness upon acute high-altitude exposure at 3,700 m in young Chinese men.

PURPOSE: We aimed at identifying the cerebral hemodynamic characteristics of acute mountain sickness (AMS). METHODS: Transcranial Doppler (TCD) sonography examinations were performed between 18 and 24 h after arrival at 3,700 m via plane from 500 m (n = 454). A subgroup of 151 subjects received TCD examinations at both altitudes. RESULTS: The velocities of the middle cerebral artery, vertebral artery (VA) and basilar artery (BA) increased while the pulsatility indexes (PIs) and resistance indexes (RIs) decreased significantly (all p < 0.05). Velocities of BA were higher in AMS (AMS+) individuals when compared with non-AMS (AMS-) subjects (systolic velocity: 66 ± 12 vs. 69 ± 15 cm/s, diastolic velocity: 29 ± 7 vs. 31 ± 8 cm/s and mean velocity, 42 ± 9 vs. 44 ± 10 cm/s). AMS was characterized by higher diastolic velocity [V d_VA (26 ± 4 vs. 25 ± 4, p = 0.013)] with lower PI and RI (both p = 0.004) in VA. Furthermore, the asymmetry index (AI) of VAs was significantly lower in the AMS + group [-5.7 % (21.0 %) vs. -2.5 % (17.8 %), p = 0.016]. The AMS score was closely correlated with the hemodynamic parameters of BA and the V d_VA, PI, RI and AI of VA. CONCLUSION: AMS is associated with alterations in cerebral hemodynamics in the posterior circulation rather than the anterior one, and is characterized by higher blood velocity with lower resistance. In addition, the asymmetry of VAs may be involved in AMS.

Polymorphisms of angiotensin converting enzyme and nitric oxide synthase 3 genes as risk factors of high-altitude pulmonary edema: a case-control study and meta-analysis.

High-altitude pulmonary edema (HAPE) is a non-cardiogenic type of pulmonary edema developing altitudes > 2,500 m. Angiotensin converting enzyme (ACE) and nitric oxide synthase 3 (NOS3) play important roles in regulating pulmonary vascular tone. To assess associations between genetic variants in the ACE and NOS3 genes and HAPE risk, 27 HAPE patients and 108 matched controls were genotyped and analyzed. The indicated HAPE association of the NOS3 G894T (Glu298Asp) single nucleotide polymorphism (SNP), which may change NO production, was further evaluated by a meta-analysis of six studies involving 399 HAPE patients and 495 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined with fixed-effects models. Stratification analyses of ethnicity and geographic location were performed. Significant associations were observed for the dominant model in two ACE tag SNPs influencing serum ACE concentrations (rs8066114 polymorphism: GG+CG vs. CC; rs4461142 polymorphism: TT+CT vs. CC). Furthermore, Single-locus analysis indicated significantly different distributions of G allele frequency between the cases (29.63%) and controls (17.13%) for the ACE rs8066114 polymorphism. The case-control distributions of genotype frequencies and T allele frequency of NOS3 G894T (Glu298Asp) polymorphism were significantly higher in the cases than controls, and the NOS3 G894T (Glu298Asp) SNP showed elevated HAPE risk under the dominant model (TT+GT vs. GG). Meta-analysis showed overall association of NOS3 G894T SNP with HAPE risk under the allele contrast and dominant genetic models, which remained significant for Asians. In conclusion, ACE rs8066114 and rs4461142 and NOS3 rs1799983 (G894T) polymorphisms may be associated with increased HAPE risk in Asians.

Anxiety correlates with somatic symptoms and sleep status at high altitudes.

High altitude exposure results in many physical and psychological discomforts, with anxiety and sleep disturbances being the most common ones. This cross-sectional study was performed to explore the relationship between anxiety, somatic symptoms, and sleep status at high altitude. A sample of 426 young males between 18 and 24 years old ascended from low-level land to 3600 m, where they acclimated for 40 days, before ascending to 4400 m. Questionnaires including the Louise Lake Score (LLS, for diagnosis of acute mountain sickness [AMS]), the Self-rating Anxiety Scale (SAS), the Epworth Sleepiness Scale (ESS), and the Athens Insomnia Scale (AIS) were administered immediately before departure from 3600 m (40th day) and the day after arrival at 4400 m (20 days after the first data collection). Physiological parameters were also measured. We observed that 49 of 426 and 51 of 329 people were diagnosed with anxiety according to SAS at 3600 and 4400 m, respectively. Physical symptoms were more severe in subjects with anxiety, and the severity of anxiety was significantly positively correlated to the severity of insomnia and increased heart rate (HR). Overall, these data indicate that after 40 days acclimatization in 3600 m, anxious persons have more severe somatic symptoms. When ascending to higher altitudes, these individuals are more likely to develop AMS, show more severe symptoms, and are prone to insomnia and more serious daytime sleepiness. Insomnia and elevated HR are indicators of anxiety severity.

[Change of Rho kinase activity in brain tissue in high altitude condition and its relationship with high altitude cerebral edema: experiment with rats].

OBJECTIVE: To observe the change of Rho kinase activity in brain tissue in the high altitude condition and its relationship with blood brain barrier permeability and high altitude cerebral edema (HACE), and to explore the pathological mechanism of HACE. METHODS: 30 Wistar rats were divided randomly into 3 equal groups, high altitude (HA) group put in low pressure cabin mimicking high altitude of 7000 m for 24 hr and then gradually exposed to higher pressure until the normal pressure, fasudil group undergoing intraperitoneal injection of fasudil hydrochloride 30 mg/kg, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, and then treated as the HA group, and normal control group (HC group). Five rats from each were decapitated with their brains taken out. The ratio of dry brain weight and wet brain weight was calculated. Western blotting was used to detect the expression of ROCK. Another 5 rats from each groups underwent injection of sodium fluorescein into the caudal vein and then the rats were decapitated to examine the natrium (sodium) fluorescence index (NaFI) of the central brain slice so as to observe the blood brain barrier permeability. RESULTS: The ROCK activity in brain tissue, ratio of dry and wet brain weight and NaFI of the HA group were significantly higher than those of the HC group (all P<0.001), and ROCK activity in brain tissue, ratio of dry and wet brain weight and NaFI of the fasudil group were all significantly lower than those of the HA group (all P<0.001) and not significantly different from those of the HC group (all P>0.05). CONCLUSIONS: ROCK in brain tissue is activated in high altitude condition, which may play a key role in the development of HACE.

[Triplex-forming oligonucleotide inhibits the expression of tissue factor gene in endothelial cells induced by the blood flow shear stress in rats].

AIM: To study the effect of antiparallel phosphorothioate triplex-forming oligonucleotide (apsTFO) matching with the shear stress response element (SSRE) of tissue factor (TF) gene promoter region on the expression of TF in endothelial cells (ECs) of rat common carotid artery stenosis. METHODS: The model of common carotid artery middle segment stenosis was established by silica gel pipe loop ligation in SD rats. The mRNA expression and protein synthesis of TF, early growth response-1 (Egr-1) and specificity protein 1 (Sp1) were measured by in situ hybridization (ISH) and immunohistochemistry (IHC) technique. GT21-apsTFO, GT20-apsTFO, GT20-psTFO and FITC-labeled apsTFO, matching with the SSRE of TF gene promoter region, were designed, and intravenously injected into rats at 0.5 h before operation. TFO was detected 4 h after the operation, and the mRNA expression and protein synthesis of TF, Egr-1 and Sp1 were detected 6 h after the operation. RESULTS: There were much fluorescence in vascular tissue, especially in the nuclear of ECs 4.5 h after the injection of apsTFO. The mRNA expression and protein synthesis of TF reduced by 22% - 23% with injection of GT20-apsTFO 6.5 h after stenosis (P < 0.01) and by 10% - 11% with GT21-apsTFO at the same time (P < 0.05). The inhibition by GT20-apsTFO was stronger than that of the GT21-apsTFO (P < 0.05). The expression of TF was not inhibited by the GT20-psTFO (P > 0.05). The mRNA expression and protein synthesis of Egr-1 and Sp1 did not change in the rat treated with GT20-apsTFO, GT20-psTFO and GT21-apsTFO (P > 0.05). CONCLUSION: apsTFO could mero-inhibit the expression of TF gene but could not change the expression of Egr-1 and Sp1 protein.

[The study of the effect of the administration of mannitol on flash visual evoked potentials].

OBJECTIVE: To study the relationship between the change of N2 wave in flash visual evoked potentials (fVEP) and the intracranial pressure after the administration of mannitol. METHODS: Fifty-two patients with elevated intracranial pressure were chosen and are divided into two groups: the former (n = 32) were treated with mannitol, the latter (n = 20) were treated with mannitol and glycerol and sodium chloride injection. The latency and amplitude of N2 wave of fVEP was measured by NIP-200 noninvasive intracranial pressure apparatus before and after the 1st, 4th, 10th administration of mannitol. RESULTS: The latency of N2 wave began to reduce at 30 min after the injection of mannitol and was lowest at 2 h. At 4 h after the injection of mannitol, the latency of N2 wave increased but was still shorter than that before the injection of mannitol. The amplitude of N2 wave did not change significantly. The reduction of the latency of N2 wave after the administration of mannitol decreased with the multiple mannitol injection. The latency of N2 wave did not change significantly after the administration of mannitol when combined with glycerol and sodium chloride injection. CONCLUSION: The latency of N2 wave of fVEP changes after the administration of mannitol, which suggests that the change of the latency of N2 wave of fVEP can reflect the change of intracranial pressure.